The exposure of eukaryotic cells to mutagenic and carcinogenic agents produces various molecular lesions in the DNA molecules. Base damages are either repaired by excision repair or they induce gaps in nascent DNA which are repaired by a post-replication repair mechanism. Phorbol myristate acetate, which inhibits excision repair, is a powerful co-carcinogen. Caffeine, a post replication repair inhibitor interacts synergistically with some mutagens and carcinogens to be an anti-mutagen. The hypothesis set forth in this proposal is that post-replication repair is necessary for mutagenesis and that mutagenesis is responsible for some carcinogenic events; further, genetic or environmental inhibitors of excision repair ought to act as powerful " co-carcinogens" by enhancing the amount of post-replication errors to occur. We propose to characterize the frequency of ultraviolet light and chemical carcinogen-induced mutation frequencies in excision repair-inhibited Chinese hamster and human lymphoblastoid cells. These studies might provide insight into the molecular mechanism of mutagenesis and co-carcinogenesis.